| Project/Area Number |
16K18918
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Drug development chemistry
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| Research Institution | Kobe Gakuin University |
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Principal Investigator |
Inoue Masaki 神戸学院大学, 薬学部, 助手 (80757097)
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| Research Collaborator |
TSUNODA Shinichi
KAMADA Haruhiko
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 腫瘍壊死因子 / TNF / アンタゴニスト / TNFR1 / 自己免疫疾患 / 一本鎖化 / 構造最適化 / 蛋白質工学 / 機能性人工タンパク質 / 最適化 |
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| Outline of Final Research Achievements |
We have been investigating the use of TNFR1-selective antagonistic TNF mutant (R1antTNF) to reveal the pharmacological effect of TNFR1-selective inhibition as a new therapeutic modality. This study aimed to further improve and optimize the activity and behavior of this mutant protein both in vitro and in vivo. Especially, we examined a trimeric structural fusion of R1antTNF, formed via the introduction of short peptide linkers, as a strategy to enhance bioactivity and molecular stability. The trimeric fusion, referred to as single-chain R1antTNF (scR1antTNF), was found to retain in vitro molecular properties of receptor selectivity and antagonistic activity but displayed a marked increase in thermal stability. Furthermore, molecular modification of scR1antTNF using polyethylene glycol (PEG) significantly prolonged the residence time in vivo. Therefore, scR1antTNF is considered useful for therapeutic drug application.
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